Effective at prevention of PONV if given at the start of anaesthesia, although not effective rescue therapy
Reduces both incidence and severity of PONV, as well as the need for additional anti-emetics
May not reduce incidence of 'clinically significant' PONV, a patient-reported outcome reflecting patient experience (BJA, 2022)
Low doses may be as effective as higher doses
Analgesia
Prolongs the duration of analgesia from regional and neuraxial techniques
Benefits mostly apply to upper limb blocks
Prolonged duration of sensory block with reduced pain intensity at 24hrs, but not 48hrs
Effect seen regardless of whether dexamethasone given IV or perineurally
Lower doses may be as effective as higher doses
May have a small intrinsic analgesic effect (BJA, 2013)
May carry an increased risk of persistent post-operative wound pain at six months (BJA, 2023)
Reduction of oedema including airway oedema and cancer-associated oedema
Replacement therapy in glucocorticoid deficient states or sick day rules
Immunosuppression e.g. IBD
Chemotherapy in certain cancers e.g. lymphomas
Dosing
Anti-emesis and analgesia: 0.15mg/kg IV single dose (4 - 8mg PO / 3.3mg - 6.6mg IV)
Airway swelling: 6.6mg IV TDS
Metastatic cord compression: 16mg daily in divided doses
Presentation
2mg tablets
3.3mg/ml clear, colourless solution stored in glass vials at room temperature for IV use
As creams for topical use
Precise mode of action as an anti-emetic and analgesic adjunct not well understood
May involve:
Endogenous prostaglandin antagonism via inhibition of cylco-oxygenase and lipoxygenase enzymes
Stimulation of endorphin release and altered spinal cord nociceptive processing
Suppression of substance P and CGRP release from nerve endings
Reduced gastrointestinal 5-HT secretion
Absorption
Peak plasma levels within 5mins of administration
Time to onset of effects 1-2hrs
Distribution
77% protein bound
Metabolism
Slow hepatic metabolism
Elimination
Excretion mainly renal as unconjugated steroids
Plasma half-life largely irrelevant as effects outlast plasma levels
Biological half life approximately 48 - 72hrs
Cardiovascular
Positive effect on myocardial contractility
Can increase vasomotor tone and effect of vasopressor drugs by increasing number of ɑ1 and β-adrenoreceptors
Prevents oedema formation by reducing capillary wall permeability
Neurological
Increase CNS excitability, which may manifest as insomnia and hyperexcitability, particularly in the elderly
No significant difference in post-operative delirium or post-operative cognitive dysfunction when dexamethasone used
Improved QoR-40 scores
Analgesia as above
Renal
Increases urinary calcium excretion
Increased GFR
Has minimal mineralocorticoid activity
Glucose control
Concerns over erratic glycaemic control, especially in diabetics, are largely disproven
The PADDAG trial showed neither 4mg nor 8mg of dexamethasone induced greater hyperglycaemia than placebo in patients, be they non-diabetic or well-controlled diabetics
The maximal perioperative glucose after 8mg dexamethasone was related to the baseline HbA1c value in a concentration dependent fashion
Blood glucose and insulin use was a tertiary outcome of the PADDI trial, which demonstrated:
Those receiving dexamethasone had higher levels of blood glucose compared to baseline, but the difference vs. placebo was small (~1mmol/L)
No difference in incidence of hypoglycaemic events
RR 3.66 of hyperglycaemia (>10mmol/L) in non-diabetic patients (although overall numbers low; 0.6% in the dexamethasone group)
RR 4.74 of insulin requirement in non-diabetic patients (although overall numbers low; 0.5% in the dexamethasone group)
Gastrointestinal
Single dose not associated with common side effects of chronic steroid use
Reduces GI absorption of calcium
Chronic use associated with multiple effects, including peptic ulcer disease
Metabolic
Gluconeogenesis and increased peripheral uptake of glucose
Lipolysis
Inhibits conversion of amino acids to proteins, causing a negative nitrogen balance
Acute withdrawal of long-term use can cause Addisonian crisis
Immunological
Wound infection
The PADDI trial found a single dose of 8mg dexamethasone was non-inferior to placebo with respect to risk of surgical site infection at 30 days
Other trials have not demonstrated an increased risk of wound infection or poor wound healing with (even high dose) perioperative steroids
Immunosuppression
Reduce the adaptive immune response for up to 48hrs, but little effect on the innate response
Some concern this immunosuppression could worsen outcomes following surgery for cancer, but to date (admittedly poor quality) studies support either no effect or potentially some benefit